Lymphocytes of B-cell lineage, with the proper cellular signals, ultimately mature into cells which secrete immunoglobulin molecules. Cell lines of B-cell lineage have been commonly produced by infecting cells with Epstein-Barr virus, but this technique produces cell lines at the B-cell stage of development which are not of tumor cell origin. While pre-B-cell lines such as REH and NALM-6 have been described, more mature B-cell lines which have not been Epstein-Barr virus-infected have been more difficult to obtain. Generally, most of the work on plasma cells has depended upon short-term culture of plasma cells from the bone marrow of patients with multiple myeloma. These cells live weeks to months in vitro.
While a number of tumor cell antigens have been described for epithelial cell tumors, few have been described for B-cell lineage malignancies. Many of these cells will express protein antigens on their surface during the active growth characteristic of malignant cells. In general, however, these antigens have proven to be upregulated receptors for cytokines (interleukin-2 and transferrin as examples) and not antigens unique to the tumor per se.
A cascade of events occurs which leads to the induction and maintenance of T- and B-lymphocyte activation. In general, these events are the result of the encounter, by T-cells, of a variety of stimuli. In vitro, stimuli which induce proliferation include mitogens, antibodies to specific T-cell receptors (such as to the T3 receptor) or reactivation of a subset of normal circulating lymphocytes by previously-encountered antigen (immunologic memory). With stimulation of these memory cells, a variety of surface proteins is expressed which participate in cellular activation and adhesion events. In general, these proteins are not unique to memory cells and can also be induced on the surface of nonmemory lymphocytes upon activation. The identification of a cell surface antigen which is uniquely associated with cells participating in the immunological memory response would be valuable for lymphocyte subpopulation manipulation in vitro and in vivo.